Merck & Co Inc

NYSE:MRK

Earnings Call Transcript 2018-Q4

[Operator]

Good morning. My name is Darla, and I will be your conference operator today. At this time, I would like to welcome everyone to Merck's Fourth Quarter 2018 Sales and Earnings Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] Thank you.

I would now like to turn the call over to Teri Loxam, SVP, Investor Relations and Global Communications. Please go ahead.

[Teri Loxam, IR]

Thank you, Darla, and good morning. Welcome to Merck's Fourth Quarter and Full Year 2018 Conference Call. Today I'm joined by Ken Frazier, our Chairman and Chief Executive Officer; Rob Davis, our Chief Financial Officer; and Dr. Roger Perlmutter, President of Merck Research Labs, who will each have prepared remarks. In addition, I’m joined by Mike Nally, our new Chief Marketing Officer and Frank Clyburn, our new Chief Commercial Officer who will both be available for the Q&A portion of the call.

Before I turn the call over to Ken, I'd like to point out a few items. You will see that we have items in our GAAP results, such as acquisition-related charges, restructuring costs, and certain other items. You should note that we have excluded these from our non-GAAP results and provide a reconciliation of these in our press release. We have also provided a table in our press release to help you understand the sales in the quarter for the business units and products.

I would like to remind you that some of the statements that we make during today's call may be considered forward-looking statements within the meaning of the Safe Harbor Provision of the US Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of Merck's management and are subject to significant risks and uncertainties.

If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Our SEC filings including Item 1A in the 2017 10-K, identify certain risk factors and cautionary statements that could cause the company's actual results to differ materially from those projected in any of our forward-looking statements made this morning. Merck undertakes no obligation to publicly update any forward-looking statements. You can see our SEC filing as well as today's earnings release on merck.com.

Finally, similar to last quarter, we have posted a presentation to the investor section of Merck.com, which highlights some of our financials from the quarter and the year.

With that, I'd like to turn the call over to Ken.

[Ken Frazier, Chairman and CEO]

Thank you, Teri. Good morning and thank you all for joining the call. In 2018, Merck distinguished itself through its strong performance across its businesses, perhaps most significantly, our full year results demonstrate that our strategy to be the premier research intensive biopharmaceutical company is working. The investments we've made in R&D over the past several years and our commercial execution have culminated in the highest top and bottom line growth the company has seen in years and we expect our momentum to carry over into 2019. At its core, Merck is a science driven organization, motivated by a quest to improve human and animal health. We've spent the last several years, reinvigorating our labs, investing in three new research centers in South San Francisco, Cambridge, Massachusetts and London and refocusing our efforts on creating truly differentiated medicines that help solve big health problems for now and the future.

This unwavering commitment to science and innovation enables us to retain the best talent in the industry, to drive our strategic priorities and to continuously enhance our pipeline of medically significant treatments and vaccines. Our clinical and commercial execution in the IO space has further separated KEYTRUDA from its competition and our leadership in oncology is further bolstered by the growth prospects for LYNPARZA and LENVIMA.

GARDASIL is not only driving meaningful growth for the company after a decade on the market, but is also instilling optimism around the world that this vaccine could help prevent and maybe eliminate certain HPV related cancers. We are confident in our broad portfolio of market leading products and our diversified high potential pipeline, which includes significant innovations in oncology, vaccines and other special – and hospital care along with a robust industry leading animal health business. In fact, Merck is one of the broadest and most promising pipelines we've had over the past two decades.

In summary, we are excited by our progress, our pipeline and our future. We are energized by the work that we do and most importantly by our ability to help patients around the world while also creating sustainable long term growth and strong shareholder returns.

Before I turn the call over to Rob, I'm pleased to announce that we will be hosting an investor event on June 20 during which we will provide an update on our strategic progress and outline how Merck will continue to deliver innovative science and create value for all of our stakeholders. We'll be back to you with the details on location and other logistics, but we ask that you save the date.

Now, I'd like to turn it over to Rob for more color on our financial and operational performance. Rob?

[Rob Davis, CFO]

Thanks, Ken and good morning, everyone. Please note that my comments today will be on a non-GAAP basis. Our results in 2018 reflects strong execution across our key growth pillars, focused investment in our pipeline and disciplined expense management. We achieved meaningful top and bottom line growth and we also executed important business development transactions initiated in expanded capital expenditure program to increase our manufacturing capacity and return additional value to shareholders through increased dividends and share repurchases. We believe our company is well positioned to achieve future growth and as our 2019 guidance shows, we expect the recent momentum in our business to continue, as we execute on our growth pillars and invest in R&D, while remaining disciplined in our allocation of resources.

Turning to our fourth quarter results, total company revenues were $11 billion, an increase of 8% year-over-year, excluding exchange with strong growth in both our human health and animal health businesses. Human health revenues increased 8% ex-exchange to $9.8 billion, led by key products in our oncology, vaccines and hospital and specialty businesses. In oncology, KEYTRUDA sales exceeded $2.1 billion this quarter, extending the unprecedented launch of this foundational therapy and solidifying Merck as the clear market leader in renal oncology, with continued strong future growth prospects.

Global growth was primarily driven by higher use in first line non-small cell lung cancer and utilization remained strong across the breadth of our indications, including melanoma, head and neck, bladder and MSI-high cancers. We're seeing strong uptake in squamous non-small cell lung cancer in the US where a good portion of newly diagnosed patients are now receiving either KEYTRUDA as monotherapy or in combination with chemotherapy, following the approval of KEYNOTE-407 in October. In total, in the US, we now have 15 approved indications and are approved in 10 different tumor types overall plus a pan tumor approval in MSI-high patients.

In ex-US markets, first line lung is the key driver of growth, mostly due to further uptake of our monotherapy indication and PD-L1 high expressors, following reimbursement approvals around the world. In Europe, we're off to a great start launching the chemo combo in non-squamous patients, following approval of KEYNOTE-189 last September. We are already seeing adoption in select markets, such as Germany where reimbursement begins upon approval and we will be working through the reimbursement process in other major European markets throughout this year.

Growth in Japan remains robust and we're very pleased with the recent approval of five new indications across lung, adjuvant melanoma and MSI-high cancers. Finally in September, we launched KEYTRUDA in metastatic melanoma in China, which will be an important market for the brand going forward, as we pursue additional indications. Overall, we remain very confident in the long term growth potential for KEYTRUDA based on increased utilization and currently approved indications and our expectation of additional approvals worldwide.

We also remain very encouraged by the progress and potential of both LYNPARZA and LENVIMA in partnership with AstraZeneca and Eisai respectively. LYNPARZA growth this quarter was driven by continued uptake in ovarian and breast cancers as well as launches in new markets such as Japan and China. In the United States, across all tumors, LYNPARZA leads the PARP inhibitor class with over 50% total patient share. We're excited by the earlier than expected US approval of SOLO-1 and look forward to bringing this treatment to more women with ovarian cancer. Growth for LENVIMA reflected strong performance in hepatocellular cancer, following recent launches in US, Europe and more recently China. Performance in Japan remains strong with LENVIMA being used in a vast majority of hepatocellular patients.

Turning to vaccines, we have a significant and innovative portfolio. Our vaccines business reflected strong worldwide demand for GARDASIL, which achieved sales of over $800 million this quarter. Health systems worldwide continued to support increased immunization with GARDASIL with the goal of reducing the incidents of certain HPV related cancers. Growth this quarter was driven by strong uptake from our recent launch in China as well as increased demand in Europe, given the move towards more gender neutral vaccination programs. Sales of GARDASIL also grew in the US, mostly reflecting the difference in quarterly phasing of public sector purchases last year. Our hospital and specialty business was led by BRIDION, where growth in the US reflects continued strong demand. BRIDION sales approached $1 billion for the year and we remain confident in the potential for additional future growth.

Looking now at our animal health business, we again saw strong growth this quarter with revenues increasing 11% to $1 billion, excluding exchange. Growth was driven by our broad portfolio with inline and newly launched products with companion animal products growing 16% and livestock sales growing 8%, both excluding exchange. Companion animal growth was driven by sales of vaccines while livestock benefited from increased sales of swine and poultry products. Animal health segment profit were $387 million in the fourth quarter, an increase of 16%, excluding exchange compared to the prior year. Our animal health business continues to perform well and we view it as a key pillar of Merck’s future growth. We continue to invest in new product development and launches and recently announced the acquisition of Antelliq, which will establish Merck as a leader in animal identification and monitoring, one of the fastest growing parts of the animal health industry.

Turning to the rest of our P&L, gross margin was 75% in the quarter. The increase of 70 basis points versus the fourth quarter of 2017 was largely due to the favorable impacts of product mix this year and manufacturing variances related to the cyberattack that negatively impacted last year. This increase was partially offset by other headwinds, such as lower prices and catch up amortization of sales milestones, primarily related to the earlier than expected approval of SOLO-1. Operating expenses of $4.8 billion increased 1% year-over-year, including a favorable 1 percentage point impact from foreign exchange.

Investments in oncology and vaccines clinical development portfolios as well as our discovery efforts drove the increase in R&D while SG&A remained relatively flat. Our tax rate of 22.5% for the quarter was 720 basis points higher year-over-year, reflecting a true up of our full year tax rate due to our mix of earnings. Taken together, we delivered earnings of $1.04 per share, an increase of 11%, excluding exchange.

Now, let's turn to our outlook for 2019. We remain confident in both our near and long term prospects for revenue growth, notwithstanding expected headwinds from price, foreign exchange and pressures on our mature and LOE products. For 2019, we expect full year revenues of $43.2 billion to $44.7 billion, which represents 2% to 6% growth, driven by strength in our key growth killers across oncology, vaccines, hospital and specialty as well as animal health.

This range assumes an approximately 1 percentage point negative impact on foreign exchange, using mid-January rates. We expect our gross margin to be roughly flat year-over-year. As we've previously communicated, we believe tailwinds, including improved product mix, will generally be offset by headwinds, including lower prices, royalty payments, fluctuations in FX and the continued amortization of collaboration milestones. We expect our operating expenses to increase year-over-year at a low to mid-single digit rate with continued disciplined management of SG&A, allowing for meaningful further investment in R&D to capitalize on our pipeline opportunities.

We expect our tax rate to be between 18.5% and 19.5% for the full year. We project average diluted shares outstanding to be approximately 2.58 billion for 2019. Taken together, we expect EPS to be between $4.57 and $4.72, including an approximately 1 percentage point positive impact from foreign exchange at mid-January rates. This would represent approximately 5% to 9% bottom line growth.

Before concluding, it's worth mentioning that our 2019 EPS guidance assumes that our other income and expense line will be roughly 0 in 2019. Due to an accounting standard implemented in 2018, we now recognize unrealized gains and losses related to our investments in equity securities and other income and expense. Based on current market conditions for our investment portfolio, we have assumed a negative impact from our equity investments in OIE in our guidance. We also expect higher net interest expense, given our cash and debt balances and given current interest rates. Market movements couldn't create additional volatility as we move through the year and we will continue to give you updates as we move forward.

In summary, we delivered strong performance in 2018. While 2019 continues to be another important investment year for R&D, we expect operational momentum across our growth pillars combined with disciplined resource allocation to deliver another year of meaningful top and bottom line growth as well as operating leverage. Longer term, we remain confident in our ability to drive strong sales growth and meaningful operating margin expansion. Our dedication to innovation and continued execution allow us to sustainably deliver for the patients we serve and in turn creates significant shareholder value.

With that, I'd like to turn the call over to Roger.

[Roger Perlmutter, President, Merck Research Labs]

Thanks, Rob. As outlined in our press release, the fourth quarter was an especially productive period for Merck Research Laboratories, marking the climax of what was an extremely busy year. Beginning first with KEYTRUDA, during the fourth quarter, we obtained 3 new indications in the United States, first for the first line treatment for patients with metastatic squamous non-small cell lung cancer in combination with [indiscernible] based upon the results of the KEYNOTE-407 trial.

Second for the second line treatment of hepatocellular carcinoma in patients who’ve previously been treated with sorafenib and third for the treatment of adults and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma probably or skin cancers. Separately and based on the results of our KEYNOTE-054 study, which was conducted with the European Organization for the Research and Treatment of Cancer, the European Commission approved KEYTRUDA for the adjuvant treatment of stage 2 melanoma with lymph node involvement in patients who have undergone successful tumor resection.

Meanwhile in Japan, we obtained five new KEYTRUDA approvals at the end of December, including the first approval based on our KEYNOTE-042 trial for KEYTRUDA monotherapy in patients with non-small cell lung cancer, whose tumors contain greater than or equal to 1% of malignant cells, expressing that PD-L1 biomarker. Data from KEYNOTE-042 are also under review in the EU and in the United States for submission of additional data results and an extension of the PDUFA data by 3 months to April 11 of this year.

Our other cancer programs also advanced meaningfully in the fourth quarter, in collaboration with our colleagues at AstraZeneca, we gained FDA approval for LYNPARZA as maintenance treatment for patients with advanced ovarian fallopian tube or primary peritoneal cancer who have experienced complete or partial response to first line platinum based therapy and whose tumors contain deleterious or suspected deleterious, germ line or somatic mutations in BRCA-1 or BRCA-2 gene. This approval is based on data presented last fall at the European Society for Medical Oncology meetings from the SOLO-1 trial.

We continue to see very positive results across our oncology portfolio, including the success of our KEYNOTE-181 trial, testing KEYTRUDA monotherapy in the second line treatment of advanced or metastatic esophageal or gastro-esophageal junction carcinoma with a 31% reduction in the risk of death as compared to traditional chemotherapy in patients whose tumors express the PD-L1 biomarker with a combined proportion score of greater than or equal to 10. This is the first demonstration of an improvement in overall survival in esophageal gastric malignancy through immunotherapy. Data from the study were presented to the ASCO GI meeting in January and have been submitted for regulatory review.

During the fourth quarter, we also announced the results of our KEYNOTE-426 trial, combining KEYTRUDA with Pfizer’s axitinib in the first line treatment of renal cell cancer as compared with sorafenib treatment. Data from this study in which improvements in overall survival, progression free survival and overall response rate were demonstrated, have also been submitted for regulatory review. Progress has been made in other disease categories as well.

For example, the FDA granted priority review with a PDUFA date of July 16 for a novel anti-microbial agent MK-7655A, which combines a new chemical entity, Relebactam with imipenem, thus blocking the activity of a bacterially expressed beta-lactamase that would otherwise inactivate imipenem. This represents an important advance in the struggle to control antibiotic resistance. We’re also active on the business development front, joining with colleagues at MGM Biopharmaceuticals to advance MK-3655, a highly selective phase 2 monoclonal antibody, directed against the FGF receptor 1 to see beta close receptor complex for the potential treatment of nonalcoholic steatohepatitis.

Our vaccine programs also progressed during the fourth quarter. At the end of the quarter, for example, we announced a collaboration with Instituto Butantan on the development of vaccines to protect against dengue virus infection. Instituto Butantan is currently conducting a Phase 3 study in Brazil with their vaccine candidate, while our own related dengue virus vaccine showed promise in the earlier phase 1 study. Finally, we commenced a rolling BLA submission for V920, our investigational vaccine designed to protect against infection with the Zaire strain of Ebola virus. We continue to provide tens of thousands of doses of this vaccine to the World Health Organization to assist them in the battle to contain an Ebola outbreak in the Democratic Republic of the Congo. We hope that through the important work of governmental and non-governmental agencies and in part as a result of our V920 vaccine, it will be possible to bring this very serious Ebola outbreak under control in the near future.

Now, my colleagues and I will take your questions.

[Teri Loxam, IR]

Thanks, Roger. Darla, we will get started on questions. I just wanted to remind everyone to try to keep their questions to a maximum of 1 to 2 to get as many people on the call as possible. So with that, I’ll turn it over to questions.

[Operator]

[Operator Instructions] Your first question is from Seamus Fernandez with Guggenheim.

[Seamus Fernandez, Guggenheim]

Thanks very much for the question. So my first question is for Ken and my second is for Frank and Roger. Ken, can you just help us understand the core areas of focus for potential M&A or business development to bolster the Merck pipeline and maybe if you could just kind of give us a general sense of areas where -- areas of interest and perhaps even the range, obviously lots of questions around the current mega cap M&A that's occurred in recent days.

And then for Frank and Roger, can you just maybe each of you kind of characterize the key opportunities near and longer term to sustain or perhaps even accelerate the KEYTRUDA opportunity? We're seeing amazing growth in that franchise, but again we're just trying to get a sense of the key new opportunities, whether it be kidney cancer as a core opportunity or perhaps somewhat longer term in the adjuvant setting? Thanks so much.

[Ken Frazier, Chairman and CEO]

Thanks, Seamus. Let me start by saying again that business development remains an important priority for us. First and foremost, we look for those scientific innovations that we believe will enhance our pipeline, because we believe that's what's important ultimately to drive long term growth and value for shareholders. In that regard, we don't try to predetermine what therapeutic areas are best. We want to find the best science that matches up to the best opportunities to help people and that's how we go about it and I’ll remind you that we were very active last year in BD. We did about 60 transactions, spanning licensing and technology deals, clinical collaboration.

We did the collaboration with Eisai, we did the acquisition of Viralytics, which expands our early immune-oncology, [indiscernible] with the Antelliq acquisition. So again, I think what we want to do, given our strong balance sheet, is to actively look across the entire spectrum of assets across therapeutic areas to create the strongest portfolio. I’ll close by saying, we continue as we've said for years to want to focus on the kinds of deals that we can add with a minimum of disruption to our ongoing scientific efforts. So we have not really been focusing primarily on the large mega-mergers that you referred to.

[Teri Loxam, IR]

And Roger, why don’t you start on the second question around KEYTRUDA key opportunities and we can turn over to Frank for the commercial portion.

[Roger Perlmutter, President, Merck Research Labs]

Right. Seamus, thanks for the question. First of all, I think it's important from a context point of view and you know this that we're still at an early point in the development of KEYTRUDA. So, keep in mind that it's just a little over 4 years since the first indication was obtained in the United States in 2014. And in that sense, the indications are still rolling out. KEYTRUDA, as I’ve said and as you know is the first truly broad spectrum anti-neoplastic agent introduced into clinical practice with 15 indications and more coming and many of those indications have not yet been broadened around the world and Frank will have a chance to talk about that. So there's a great deal of opportunity to do good in helping patients around the world.

But beyond that, we’ve continued to work on a strategy in which we first demonstrate activity with monotherapy and different tumor types and the monotherapy studies are essentially complete. We have a few more studies coming through, but then move forward in combination studies, while simultaneously advancing from SALVAGE therapy, third line, second line to first line adjuvant, neoadjuvant and all of those studies are going on and we are expanding into new areas and in addition in combination with other agents, both those that have already been introduced into practice, axitinib in renal cell carcinoma and in addition our own pipeline.

So there is just a huge set of opportunities. Looking forward, I think as I mentioned the data that we presented in esophageal gastric cancer in January at ASCO GI and the renal cell data, which will be presented in mid-February from the KEYNOTE-426 study are special highlights, but there are going to be a lot of presentations coming forward. There's a lot of new data coming out and we'll have a chance to talk about some of that for example in advance at ASCO. It's early days, but a lot of expansion opportunities and Frank, I think you can talk about that.

[Frank Clyburn, CCO]

Seamus, good morning. And to echo Roger's point, we have actually a very early stage launch going on and I just wanted to reiterate especially outside the US for lung cancer, we are right now launching KEYNOTE-189 and we're just in the early stages of that launch. So if you look at our ex-US growth, in fact this quarter, ex-US growth was over 86% and that just shows the early progress that we're making, not only with our monotherapy, but early on with our combination in lung. In addition, we have a number of other opportunities, you heard us announce the approvals in Japan, we're very excited about the opportunity that we have in China with our second line melanoma indication and we have a broad program that we are building in China.

In addition to that, we have significant opportunities, as you've heard from Roger with regards to our renal cell carcinoma data that we're looking forward to presenting KEYNOTE-426 at ASCO GU. We’re also excited about triple negative breast cancer, we presented our data now for KEYNOTE-048 for head and neck cancer with first line chemo combination, gastric cancer and others. So we're very excited about our current indications and expanding those around the world as well as the significant amount of data readouts that are going to be coming in the future that we think will provide very significant growth, not only this year, but in the long run.

[Teri Loxam, IR]

Great. Thanks for the questions, Seamus. Darla, we’ll move on to the next one please.

[Operator]

It’s from the line of Steve Scala with Cowen.

[Steve Scala, Cowen]

Thank you. A couple of questions. Ken, I was interested in your comment that Merck has one of the most broad pipelines in the past two decades and this is quite a statement given Merck’s rich research history, what are we missing externally that Merck sees internally and will June 20th be the opportunity for us to learn a lot more about the pipeline?

And secondly, Merck’s pneumococcal vaccine, I believe received breakthrough designation in children, but not adults. Is this an issue of timing or did FDA deliberately not grant the 15 valid product breakthrough in adults? Thank you.

[Ken Frazier, Chairman and CEO]

Thank you for your question. Steve, I continue to believe that Merck’s longer term revenue growth prospects are underappreciated in large part because people don't see the pipeline the way we do. So let me try to answer your question. So we see tremendous future growth, not only in KEYTRUDA, LYNPARZA and LENVIMA, but we have behind it a formidable internal pipeline of assets in oncology over 20 unique mechanisms. In the vaccine world, we think the GARDASIL opportunity is really significant going forward, but behind that are opportunities in next generation pneumococcal, RSV, CMV, dengue and other areas are the ones that we look forward to.

As we also look beyond that, we just announced positive Phase 3 data for ZERBAXA, our antibiotic for hospital acquired and ventilator acquired pneumonia, which we believe could be a very sizable opportunity to go with our leading portfolio of hospital [indiscernible] which we acquired a couple of years ago is now being studied in phase 3 in chronic cough and [indiscernible] collaboration is just another example of that, not to mention great novel access in HIV and neuroscience. So to answer your question, I actually look forward to the June opportunity for us to talk about what it is that we see in our pipeline. I will say that we are genuinely excited, we see the opportunities for us to invest in across a broad area and again we look forward to speaking to you in more detail on June 20.

[Roger Perlmutter, President, Merck Research Labs]

Right. And with – this is Roger, with respect to the breakthrough designation, yes, we did receive breakthrough designation in pediatrics for pneumococcal conjugate vaccine. And the reason was because of the very meaningful clinical data that we obtained, demonstrating the balance response across all 15 stereotypes, represented in that vaccine. We have very strong data in the adult segment as well and it's really a matter of timing with respect to how we interact with the agency, just to remind you breakthrough designation provides a mechanism whereby you can have more frequent consultation interaction with the agency on late stage trials and keep in mind that [indiscernible] is already in 8 phase 3 studies that we'll be reading out this year, and next year. So there's already a very substantial head of steam on this program.

[Teri Loxam, IR]

Great. Thank you. Will we go to the next question please, Darla?

[Operator]

It’s from Andrew Baum with Citi.

[Andrew Baum, Citi]

Many thanks. Couple of questions please. Some of the industry lobby has championed net pricing. Given the announcement last night, to find content, could you talk to the Merck assessment of the proposal, particularly probably to go through, how you see the risk as well as the potential public service and the spillover in terms of the commercial book of business when?

And then secondly, to Roger, I know that you recently initiated a trial of olaparib in tissue agnostic setting with HRR mutated treatments who are resistant to refractory standard treatment. The question is, number one, is that trial findable, given the advanced nature of the patients and number two, the size of that patient population, depending on what biomarker you use could be very substantial. Could you talk to how large that population may be in a percentage of addressable relapse refractory patients?

[Ken Frazier, Chairman and CEO]

Thank you, Andrew. Let me start with your first question about the HHS rebate proposal. Let me start by saying we share the administration's goal of lowering out of pocket costs for patients, that's critical for patients, it's critical for our business. As you know, unfortunately, the current pharmaceutical supply chain includes various misaligned incentives that serve to support middlemen who are often neglected patients. We are evaluating the specific proposal released by the administration and we are hopeful that it will achieve the shared goal of ensuring patients have affordable access to innovative medicines.

[Roger Perlmutter, President, Merck Research Labs]

And Andrew, I think you were asking a question and I'm having a little bit of trouble hearing you here, but you're asking a question about a LYNPARZA study, which was a tissue agnostic study and again this is part of the broader rollout of our LYNPARZA analysis because what we found with LYNPARZA as I think everyone recognizes is that the rate of activity of LYNPARZA is greater than we expected. First of all, any DNA repair, a variety of DNA repair defects, defects in homologous recombination seem to sensitize cells to LYNPARZA, but even in cell types in which those defects are not recognizable, there's evidence, accumulating evidence that we're seeing clinical responses. So we're beginning to think of LYNPARZA of having much broader activity and that's particularly the case when we look at LYNPARZA in combination with KEYTRUDA and other agents. So you can expect to see broader studies of LYNPARZA in a variety of different settings, both outside of the hormone responsive tumors and as well in combination with other agents. I hope that helps.

[Teri Loxam, IR]

Great. Thanks, Andrew. We’ll move on to the next question please, Carla.

[Operator]

Your next question is from Chris Schott from JPMorgan.

[Chris Schott, JPMorgan]

I guess my first question was just on longer term margin expansion and just expenses in general. I guess, so when you think about the low to mid-single digit OpEx growth in 2019, is that a reasonable growth rate to think about on a go forward basis for Merck or should we think about spending starting to moderate as we look out to 2020 and beyond? I know in general, there's been a lot of discussion around kind of the magnitude of operating margin expansion, so is there any color on that front would be helpful?

And my second question was just focusing a little bit more on the launch dynamics in first line lung, specifically in the US. I guess, can you just give us a sense of where we are at this point in terms of share of new starts and are there any additional areas for growth within the lung market and I guess where you must focus on from a commercial standpoint as we think about just that indication playing through in the US?

[Teri Loxam, IR]

Thanks, Chris. So we’ll start with Rob.

[Rob Davis, CFO]

Thanks, Chris. And to your question on long term margin expansion, so as I said in the prepared remarks, we continue to believe we will see meaningful margin expansion, operating margin expansion as we go forward, but as we've been talking about, given the fact that we have such a wealth of opportunity right now in R&D, you start with KEYTRUDA and look at just what this drug could be and how unprecedented it is, we want to make sure we're investing fully behind that as well as with LYNPARZA and LENVIMA, those programs are now in full swing, not to mention our vaccines program.

So as we've indicated, we do think you're going to see sales growth continue and with that, you're going to see R&D grow in the near term faster than sales over the next couple of years, as we really get to the bulk of that with R&D slowing down to a rate slower than sales thereafter and SG&A will continue to be managed very tightly. It's nice to see frankly that even despite the fact that we're making meaningful investments in R&D in 2019, we're actually going to see operating margin expansion in ’19, so that actually is really I think a result of what we've done from disciplined expense management [indiscernible] and then you'll see R&D slow down after we get out of the next couple of years. So that's really what will drive it.

[Teri Loxam, IR]

Okay. Thanks, Rob. Frank, we’ll have you comment on the first line lung market.

[Frank Clyburn, CCO]

Chris, we are seeing significant share of newly diagnosed first line non-squamous non-small cell lung cancer patients that do not have an abnormal EGF or gene. Based off of KEYNOTE-189, we've seen that penetration very rapidly in the majority of the segments in the non-squamous, non-small cell lung cancer setting. We do have room for further penetration in particular in the PD-L1 patient population in the US and that's where the team is focused and also we are seeing very rapid uptake with our KEYNOTE-407 approval at the end of October and we're penetrating the squamous cell carcinoma patient also very significantly. So I think in the US, I would say it's really in the PD-L1 negative population where there's opportunity for further growth in the non-squamous patients. I would highlight outside the US and just to reiterate that we're very early on in the launch outside the US in lung cancer. In fact, most of our growth outside the US is primarily being driven off of the PD-L1 high express patient population in KEYNOTE-024, so we're just rolling out our chemo combinations around the world and anticipate significant growth outside the US in lung.

[Operator]

It’s from David Risinger with Morgan Stanley.

[David Risinger, Morgan Stanley]

So I just wanted to go back to the margin opportunities beyond 2019. It seems like Merck is increasingly becoming more of a specialty focused company and to that end, many specialty biopharma companies can generate higher margins, simply because they don't need primary care infrastructure and the other costs associated with a much broader portfolio and so could you discuss opportunities to further streamline Merck’s cost structure in future years as you continue to pivot the company?

And then second, with respect to the data on February 16, the abstracts are coming out on Monday the 11 at 5 PM. So will we see the key data in the abstract release or will we really have to wait for the data on the 16?

[Ken Frazier, Chairman and CEO]

All right. Dave, thanks for the question. Maybe, I'll take the first part and then Roger can take the second part. So, as you look at the profile of the business, given the mix of our portfolio, you are correct that as we go forward, we continue to believe that there is an opportunity to shift, as we move to the more specialty focused business to continue to optimize the resources we have on primary care. I think the important point though is this isn't a new thing for us, in fact, when we pointed this out in the past, we've actually been able to grow on an EPS basis through the years even when we didn't have sales growth at the same time, we were standing up an oncology franchise from scratch and investing meaningfully into R&D.

And so, we did that because we have already started really harvesting some of the primary care resources we have in the marketplace, primarily through selling forces. We've been reducing selling forces over the last several years to be able to do that and there's opportunity for us to continue to do that going forward. That's why we do believe that we have -- we're going to continue to see SG&A get better as a percentage of sales, despite the fact that we're already at an industry best-in-class position with the fact that we still have the primary care resources in place although less than they used to be.

So that is an opportunity that's out there and we're going to be driving it over the next couple of years as we move forward. So that is something you should look for, as we go forward. I think the thing that's important to note is while we're getting the favorable impact from mix, obviously given the strong volume growth and margin you get from positive mix, we do have the headwinds at the gross margin line that we’ve talked about, that’s going to cause gross margin to be roughly flat. So the operating margin expansion we're going to see will come from that SG&A leveraging we're talking about as well as the R&D I mentioned earlier.

[Roger Perlmutter, President, Merck Research Labs]

And David, you're referring at February 16 to the renal cell carcinoma data from KEYNOTE-426. Of course, on February 16 is also the PDUFA date for the 054 study in adjuvant melanoma, but I think you're referring to the 426 data. And the complete data of course will be presented then. There will be an abstract that appears before hand, the abstract has some data and depending on what you view as key, there's some material in it. We're eager to gain publication also of the complete analysis just as soon as we can, so there will be various different parts of the data coming out, but the main presentation on the 16 is the part that I would focus.

[Operator]

It’s from Umer Raffat with Evercore ISI.

[Umer Raffat, Evercore ISI]

First, perhaps Roger, I feel like there's a trial which hasn't come up very much at all on Merck conversations, which is your stage 3 lung trial, KEYNOTE-799 and it's my understanding that it's a first line trial within stage 3, which would potentially position KEYTRUDA before the current label for infancy. However what I noticed was your slide today calls it a second line trial, so I just wanted to clarify that, a. And b, on the pneumococcal vaccine side, I know there's a couple of Pfizer patents, which you guys have prosecuted in the past and now appealing. And my question is, as it stands currently and let's say the appeal doesn't go favorably, do you have the freedom to operate?

[Roger Perlmutter, President, Merck Research Labs]

Okay. With respect to KEYNOTE-799, just to provide a higher altitude context for this, from the very beginning, our concern with respect to administering KEYTRUDA in the setting of radiotherapy has been pneumonitis and we know that from a variety of different studies previously that we had come to associate proximity of radiotherapy with KEYTRUDA administration with more inflammation in the lungs. So 799 has a safety, an important safety component, which is the administration of KEYTRUDA in combination with chemotherapy plus radiotherapy in different cohorts for the question of whether or not pneumonitis feeds 10%, because that's really an important issue. These are patients -- the actual study population is a population that has undergone resection, but is not widely disseminated. Let me get this right, the actual population is a population of individuals who have lung cancer that is radio responsive, potentially radio responsive and who can receive that in a first line environment, because they won’t receive prior systemic chemotherapy, if that was your question.

[Ken Frazier, Chairman and CEO]

And to your question with respect to V114, let me say that we continue to believe that we will have freedom to operate in that space and recently the IPR ruling from the PPAV was in the favor on a number of the patents that we have challenged. So we'll see what goes on as we move forward.

[Operator]

It’s from Tim Anderson with Wolfe Research.

[Tim Anderson, Wolfe Research]

A couple of questions. Going back to the very first line of questioning on your pipeline and the perception by investors that at least late stage tends to run on the thin side. Here you and Bristol potentially share a common thread, which is all the heavy spending in IO has may be crowded out other R&D programs. So the question I have in this context is something that we asked you maybe about a year ago, when is R&D spending on KEYTRUDA going to peak, about a year ago, you suggested that wasn't very far off qualitatively, but it was never quite clear to me what that meant, I know with all the combination programs, maybe it doesn't peak anytime soon. So that's the first question.

Second question is just on your triple negative breast adjutant trial update on timing of seeing those results and how would you characterize the riskiness of that trial in terms of achieving a positive readout. Would you say it's low or medium or high risk?

[Teri Loxam, IR]

Let's start with Rob to talk about the cost first.

[Rob Davis, CFO]

Good morning, Tim. So with R&D, so if you look at what's driving the bulk of our clinical spend right now, it is still KEYTRUDA, but it's actually now more combination studies than it is monotherapy studies, a lot of the monotherapy clinical studies are already starting to peak and come off. So really right now, what's driving it is the combination studies and then in addition to that, importantly, the investments in LYNPARZA and LENVIMA will be peaking over the next couple of years too. So, if you look at total R&D, it is being driven by those and then obviously our vaccines programs are contributing as well. So those are the main group categories and we do think though the bolus of KEYTRUDA for latest studies and the broader LYNPARZA, LENVIMA studies will peak in the next couple of years.

So when we've been talking about that threshold happening, it's really those programs that are driving that change where we do think you'll see R&D slowdown, as we move forward. Obviously though, the good news from a long term perspective is Roger keeps turning over new positive things, so we always have to moderate as we have opportunity to invest, but the good news is, we have a great pipeline, we're investing behind it and we're going to invest, you should see a peak in the next couple of years.

[Teri Loxam, IR]

Great. And Roger do you want to address the second question.

[Roger Perlmutter, President, Merck Research Labs]

Right. I believe Tim that you're referring to the KEYNOTE-522 study, which is a neo adjuvant study and we did have the opportunity to see early data from the 522 study, we had the chance to share those data with the agency and we and they agree that it is important to get additional data with a longer term follow up, so that's what we're waiting for, for those, for that study and once we have those data available, we’ll have a chance to look at it more carefully and then of course share with you.

[Operator]

It’s from Vamil Divan with Credit Suisse.

[Vamil Divan, Credit Suisse]

So one, I appreciate the color you gave on the lung cancer side and the commercial uptake there. I’m just trying to understand the adjuvant melanoma and also the front line renal indications as we need to see the full data on the labels, was there anything specific or unique with those two indications that may make the uptake faster or slower than what we've seen so far in lung cancer?

And then the second one, just going back to the topic of drug pricing, if you can just share just what you're assuming in terms of net pricing growth in the US in 2019 for your guidance and also sort of related to that question in terms of KEYTRUDA, if you can just sort of share your net pricing assumptions of US, Europe and also China would be very helpful.

[Teri Loxam, IR]

So we'll start with Frank on the adjuvant melanoma RCC and maybe you can just call it broadly on pricing for KEYTRUDA before we turn it over to Rob for the other part of the question.

[Frank Clyburn, CCO]

Adjuvant melanoma, we're actually just starting and got approval in Europe for adjuvant melanoma. We do think this is a good opportunity for us. We have established a very strong foothold in metastatic melanoma, so we think this is a good opportunity to expand into adjuvant melanoma. As Roger mentioned, we're waiting on our PDUFA date for adjuvant melanoma in the US and we think we will be competitive there as well.

With regards to RCC, we're excited about the opportunity. The study was done across all risk groups and we're looking forward to sharing the data in the next several weeks, but we think that this will be a very important opportunity in RCC upon approval.

As far as KEYTRUDA goes with regards to pricing, we don't give out specific guidance from a pricing perspective, but in the ex-US markets, we're seeing very strong reimbursement for KEYTRUDA based off of a very strong value proposition that we have and we feel as though we're positioned very well from a reimbursement perspective outside the US. And then in the US, we also feel as though we're positioned very well with regards to reimbursement, especially because KEYTRUDA is reimbursed in Part B currently.

[Rob Davis, CFO]

Good morning, Vamil. To your question on the guidance, while our guidance range does assume multiple scenarios, we don't require any additional pricing in the United States to meet our guidance range.

[Teri Loxam, IR]

Right. And we're going to try to squeeze in a few more questions. I know it’s close to the top of the hour. Next question please, Carla.

[Operator]

It’s from Jason Gerberry with Bank of America.

[Jason Gerberry, Bank of America]

Maybe just Frank, just a follow up on a couple of Vamil’s questions. So in adjuvant melanoma, just curious in lung, you enjoy a first mover advantage. In adjuvant melanoma, Bristol already has roughly 70% share, so just kind of curious how you think you can make inroads if you think the first mover advantage is really that important or if you think you can actually capture share?

And then my second question, just on frontline renal, in the US, and may be that you’re drawing from your experience that other tumor settings, are payers mandating that you -- they'll only reimburse the specific studied combinations and the reason I ask is I'm wondering if there's an advantage at all in terms of how these different TKI combinations will be used, will physicians ultimately migrate to using different TKIs which they're more familiar with and more commonly used or if there's going to be a winner takes all with potentially the study that gets there first with TKI.

[Frank Clyburn, CCO]

So in all things being equal, you would like to be first in most of the indications, however, we have experienced in several cancer types where we were not first, so I’ll point you to bladder where we actually launched fifth in the US and we now have the leading market share in bladder cancer and really it was because of the strong data with KEYNOTE-045 and the overall survival benefits. So really the oncologists are going to look first and foremost to the data and we feel as though KEYNOTE-054 is a very strong data set and we feel as though will be competitive.

The other thing I would also say is that in the community, especially in the US, because of the breadth of our program and because of the use in lung cancer in head, and neck and now in gastric and other cancer types, we feel as though the community's very familiar with using KEYTRUDA. They're giving us very strong feedback on the profile of KEYTRUDA and we think that's going to help us, not only in adjuvant mel, but also being second in renal cell carcinoma.

And then the last one I mentioned on renal cell carcinoma is when we share the data in the next several weeks, we feel as though as Roger has highlighted, we’ve top line having overall survival benefit, progression free survival benefit and strong response rate. So usually the oncologists will make a choice based off of the data they see and we're looking forward to upon approval competing in RCC.

[Teri Loxam, IR]

Great. Let’s move on to the next question please.

[Operator]

It’s from Alex Arfaei with BMO Capital Markets.

[Alex Arfaei, BMO Capital Markets]

And Roger, could you please provide your thoughts or comments on KEYTRUDA lifecycle planning. Obviously, [indiscernible] you'll be more dependent on KEYTRUDA. I realize very few years away but given your valuation on potential size of this product, it does become an important investment consideration?

And then for Frank, could you please provide your estimates of KEYTRUDA sales by indication in both US and ex-US.

[Roger Perlmutter, President, Merck Research Labs]

So the first question about KEYTRUDA, so obviously KEYTRUDA has been a winning franchise obviously for us and an important growth driver across all the opportunities that we have both as monotherapy as well as combination, but we continue to stress the fact that as we look at, we don't see ourselves as just a KEYTRUDA story. So, I’ve emphasized before the other pillars of growth, including LYNPARZA and LENVIMA in oncology, what comes after that with 20 unique mechanisms, the vaccines programs that we have, [indiscernible]. We continue to think that even when we see an important drug like JANUVIA go off patent that Merck will have multiple sources of growth going forward. And then of course it's really important to recognize that in addition to our internal pipeline, we're continuing to seek to augment that pipeline with value creating innovative external assets in business development. So we feel very confident about our ability to drive sustained revenue growth going forward, recognizing that a major patent expiration is coming.

[Teri Loxam, IR]

Great. We will turn it over to Frank next.

[Frank Clyburn, CCO]

In the US and this is very directional data due to the claims data lagging several months behind, but approximately 65 %to 70% of our users non-small cell lung cancer, melanoma represents about 10%, head and neck is approximately 5%, bladder approximately 5% and then we also are seeing good growth in the MSI-high agnostic indication that represents about 5% of our business and then the all other category or other indications represents about 10%. Outside the US, it's really hard to get specific breakdowns, but the majority of our use right now is in lung cancer.

[Teri Loxam, IR]

Great. Thanks, Frank. So to get to our last question.

[Operator]

It’s from Geoff Meacham with Barclays.

[Geoff Meacham, Barclays]

Frank, I want to get a bit more detail about the OUS dynamics for KEYTRUDA in lung, you guys saw good trends in 4Q. But I wasn't sure if we're already at an inflection point based on the cadence of reimbursement, maybe just be helpful to go through how you see the pace of share gains in Europe in lung over the balance of the year?

And then Roger at a higher level, how are you guys thinking about the balance of therapeutic areas in the pipeline. I mean obviously, you want to press your advantage in oncology, but is expanding other existing categories a strategic priority or is there a capacity for a new therapeutic category?

[Frank Clyburn, CCO]

So in Europe, I'll give an example. So right now, we have reimbursement in most of the European Union for KEYNOTE-024 and that's where you're seeing a lot of the growth on our monotherapy indication. With 189, we have reimbursement in Germany, Austria, Netherlands and a couple of other markets, but we're very early on in getting an uptake for 189 broadly in Europe and I anticipate that will come throughout the year, very similar ramp to what we saw back when we launched KEYNOTE-024. So think of that, the timing you should be thinking about for that ramp.

In addition to that, as mentioned, Japan we think is a very significant opportunity now with not only the approval of 189, but 407 and also KEYNOTE-042. So we think Japan provides a very good opportunity outside of the US. And then as mentioned, we're in the very early stages in China with just our first launch in second line melanoma, so we see also outside the US, significant opportunities for growth there.

[Roger Perlmutter, President, Merck Research Labs]

Yeah. And this is Roger, if I might I’d say also today, the PHMP announced that they adopted a positive opinion with respect to 407 in Europe, so that of course reimbursement will be required in most markets and will take some time, but it's going to advance that still further. In terms of the balance of therapeutic areas, Geoff, our interests, certainly my interest is in having the greatest possible impact on improving and extending human life wherever we see that and so we're not going to be down to any particular therapeutic area.

If you look at the kinds of things that we're doing, look at the work that's taking place in HIV right now, MK-8591 is an extraordinary molecule, the Phase 2 data in combination with [indiscernible], we hope we will have an opportunity to present those data probably sometime around the middle of the year and this is really a remarkable compound in terms of its potency, the durability of the treatment effect and it changes the landscape in a lot of ways in terms of how you think about HIV treatment. That's a therapeutic area which doesn't get enormous amount of tension externally, but which we're putting a lot of effort into, just as we're putting a lot of effort into other areas. So, there's a lot of work going so.

[Ken Frazier, Chairman and CEO]

So let me close by thanking for joining us. We had a strong 2018. We're confident going forward in our execution and our pipeline and our future. We believe that we're well positioned to drive sustained revenue growth and we also expect meaningful operating margin expansion over time and that's largely the result of a differentiated pipeline that we believe will actually position Merck well going forward. So thank you.

[Teri Loxam, IR]

That concludes our call. Thank you, Darla. Thanks, everyone.

[Operator]

Thank you. This concludes the Merck Fourth Quarter 2018 sales and earnings conference call. You may now disconnect.